A variety of control mechanisms are exerted at the level of the primary afferent fiber terminal modulating the transmission of sensory impulses coming from the periphery. Previous investigations of the subject have largely focused upon the role of gamma-amino-butyric acid, the transmitter responsible for depolarizing afferent teminals and for presynaptic inhibition. However, much recent work indicates that control of afferent inputs is a far more complicated process than has hitherto been thought. The overall objective of the present investigations is to understand some of the ways by which the spinal cord modulates the transmission of sensory information and the mechanisms of the processes used in such modulation. This project is designed to investigate factors influencing the properties of primary afferent fiber terminals and the release of transmitter from them. Multidisciplinary expermients will use electrophysiological, neurochemical and pharmacological techniques to study afferents in frog spinal cord and dorsal root ganglion maintained in vitro. Answers will be sought to the following: Do a variety of putative transmitters normally found in the dorsal horn of the spinal cord alter electrical properties of terminals and the release of excitatory transmitters? If so, what are the underlying mechanisms? Does the Eccles form of presynaptic inhibition exist in the frog cord? What are the effects of repetitive firing of primary afferents or their terminals? What are the mechanisms by which such repetitive activity produces after-hyperpolarizations and conduction block? One might anticipate that dysfunction of modulatory mechanisms would cause abnormalities in the functioning of the spinal cord. And indeed abnormalities of presynaptic function have been implicated in the excessive response to passive movement in spasticity in the absence of reflexes in spinal shock, in the flexor spasms of paraplegia, in the pathogenesis of tetanus and in the causation of painful states. The investigations proposed thus concern important areas in neurobiology--areas also implicated in the pathophysiology of disease states.